Relationship Between FBXO45 and Tumor Suppressor PAR-4 in Cancer

Overview

F-Box Protein 45 (FBXO45), an E3 ubiquitin ligase forms a complex with SKP1-CUL1 (SCF) to polyubiquitinate target protein prostate apoptosis response protein 4 (PAR4). Par-4 is a well-known tumor suppressor protein that exhibits potent pro-apoptotic functions in cancer cells. Although a detailed mechanism of actions of these proteins have already been established, the relationship between FBXO45 and PAR4 expression at gene and protein levels are largely unclear. To demonstrate this, FBXO45 expression was modulated by overexpression and knock-down strategies in HEK 293T cells (kidney cancer cells) while the expression of PAR4 was analyzed. Western blot, Immunofluorescence, and qRT-PCR data showed that FBXO45 overexpression decreased PAR4 and knockdown of FBXO45 by shRNA increased PAR4 protein levels in HEK293-T cells. These results support the hypothesis that FBXO45 regulates PAR4 protein levels and when FBXO45 is silenced, PAR4 signal increases and might promote apoptosis-mediated cellular events. In conclusion, further studies are needed to determine if the FBXO45-PAR4 axis could represent a prospective therapeutic target for human malignancies.

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